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Abstract

OBJECTIVE: Common variants in the Fat mass and Obesity-associated (FTO) gene are related to body mass index (BMI), which is a predictor of hip fracture risk. This study sought to examine the association between variants in the FTO gene and hip fracture risk. DESIGN AND PARTICIPANTS: This is a prospective study including 934 postmenopausal women aged 60 years and above living in Dubbo, Australia (Dubbo Osteoporosis Epidemiology Study) followed up between 1989 and 2007. MEASUREMENTS: Six SNPs (rs1421085, rs1558902, rs1121980, rs17817449, rs9939609 and rs9930506) of the FTO gene were genotyped using Taqman assay. Bone mineral density at the lumbar spine and femoral neck was measured by DXA (GE-Lunar) at baseline. Incidence of hip fractures during the follow-up was ascertained by reviewing X-ray reports. We used Cox's models to estimate the association between the genetic variants and hip fracture risk. We also utilized Bayes factor to evaluate the association. RESULTS: 102 women (11%) had sustained a hip fracture. The incidence of hip fracture was greater in women homozygous for the minor allele of all SNPs. Women homozygous for the minor allele (AA) of rs1121980 had significantly higher risk of hip fracture (hazard ratio, 2.06; 95% CI 1.17-3.62) than women homozygous for the major allele (TT). The observed data favored the hypothesis of FTO gene and fracture association over the hypothesis of non-association by a factor of 9. CONCLUSION: Common variations in the FTO gene are associated with hip fracture risk in women, and that FTO gene may help improve the predictive value of hip fracture risk. This article is protected by copyright. All rights reserved.